Shankar Venugopal K, Handa Ashok, Hands Linda
Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
J Vasc Surg. 2008 May;47(5):1033-8. doi: 10.1016/j.jvs.2007.11.030. Epub 2008 Mar 6.
Naturally occurring heparin-like activity in the form of endogenous heparin and heparin sulfate proteoglycans has been shown in normal human plasma. Exogenous low-dose heparin improves pain-free walking distance and maximum walking distance in peripheral arterial occlusive disease (PAOD). Is reduced endogenous heparin activity responsible for some of the problems found in PAOD? This study compared heparin-like activity in patients with PAOD with that in healthy subjects and explored its relationship to disease severity.
In part 1, native and heparinase-modified thromboelastography was performed on peripheral venous blood samples in three groups of patients to measure heparin-like anticoagulant activity. Group 1: 15 control subjects (median age, 60 years; range, 49-74 years; ankle-brachial pressure index [ABPI] >0.9); group 2: 14 patients with intermittent claudication (median age, 66 years; range, 56-80; ABPI, 0.69 [SD, 0.09]); group 3: 14 patients with rest pain (median age, 67.5 years; range, 54-84 years; ABPI, 0.45 [SD, 0.08]). In part 2, heparin equivalent to that in normal plasma was added to blood samples from 15 patients with short-distance claudication (n = 4) or rest pain (n = 11), and baseline (without heparinase) thromboelastography was performed to exclude lack of antithrombin as a cause of diminished heparin-like activity.
In part 1, all patients with PAOD had a significant increase in coagulability compared with controls. Heparinase-modified thromboelastography in controls showed a significant decrease in the latent period between placing the sample in the analyser, where it is recalcified, to the initial fibrin formation (DeltaR time; P = .002) compared with native TEG, confirming endogenous heparin-like activity. Using DeltaR time as a measure of heparin-like activity, a significant reduction was found in patients with claudication (0.33 minutes; 95% confidence interval [CI], 0.004-0.65; P = .02) and in those with rest pain (0.25 minutes; 95% CI, -0.02 to 0.52; P = .02) compared with that in controls (0.78 minutes; 95% CI, 0.39-1.16). The DeltaR time also correlated with the ABPI (r = 0.35, P = .02), suggesting declining heparin-like activity with increasing ischemia. In part 2, exogenous heparin restored the thromboelastography in PAOD patients to normal, suggesting that lack of endogenous heparin-like compounds rather than reduced antithrombin levels was responsible for changes in coagulation.
Patients with PAOD have reduced endogenous heparin-like activity that correlates with disease severity.
正常人体血浆中已显示存在内源性肝素和硫酸乙酰肝素蛋白聚糖形式的天然类肝素活性。外源性低剂量肝素可改善外周动脉闭塞性疾病（PAOD）患者的无痛步行距离和最大步行距离。PAOD中发现的一些问题是否与内源性肝素活性降低有关？本研究比较了PAOD患者与健康受试者的类肝素活性，并探讨了其与疾病严重程度的关系。
在第1部分中，对三组患者的外周静脉血样本进行了天然和肝素酶修饰的血栓弹力图检查，以测量类肝素抗凝活性。第1组：15名对照受试者（中位年龄60岁；范围49 - 74岁；踝臂压力指数[ABPI]>0.9）；第2组：14名间歇性跛行患者（中位年龄66岁；范围56 - 80岁；ABPI，0.69[标准差，0.09]）；第3组：14名静息痛患者（中位年龄67.5岁；范围54 - 84岁；ABPI，0.45[标准差，0.08]）。在第2部分中，将相当于正常血浆中的肝素添加到15名短距离跛行（n = 4）或静息痛（n = 11）患者的血样中，并进行基线（无肝素酶）血栓弹力图检查，以排除抗凝血酶缺乏作为类肝素活性降低的原因。
在第1部分中，与对照组相比，所有PAOD患者的凝血性均显著增加。与天然血栓弹力图相比，对照组中肝素酶修饰的血栓弹力图显示，从将样本放入分析仪（重新钙化）到初始纤维蛋白形成的潜伏期（DeltaR时间；P = .002）显著缩短，证实了内源性类肝素活性。以DeltaR时间作为类肝素活性的指标，与对照组（0.78分钟；95%置信区间[CI]，0.39 - 1.16）相比，跛行患者（0.33分钟；95%CI，0.004 - 0.65；P = .02）和静息痛患者（0.25分钟；95%CI， - 0.02至0.52；P = .02）的DeltaR时间显著缩短。DeltaR时间也与ABPI相关（r = 0.35，P = .02），表明随着缺血程度增加，类肝素活性下降。在第2部分中，外源性肝素使PAOD患者的血栓弹力图恢复正常，表明内源性类肝素化合物缺乏而非抗凝血酶水平降低是凝血变化的原因。
PAOD患者的内源性类肝素活性降低，且与疾病严重程度相关。
